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How lifestyle factors and genetics affect brain health
An international research collaboration involving Simon Fraser University (SFU) provides a clearer picture of how genetic predispositions and lifestyle factors contribute to brain health as people age.
SFU statistics and actuarial science professor Lloyd Elliott works with UK Biobank to gather insights into disease and aging. The extensive database contains anonymous genetic, lifestyle and health information from half a million volunteers, with brain imaging from over 40,000 people. Ranging in age from 44 to 82 years old, these subjects are at risk of developing age-related neurodegenerative illnesses.
The research was directed by Dr. Gwenaëlle Douaud, associate professor at the Wellcome Centre for Integrative Neuroimaging, University of Oxford. Douaud’s previous research identified a network of the brain especially vulnerable to aging, schizophrenia and Alzheimer’s disease. However, the impact of lifestyle factors and genetic influences on this network were unclear.
Their current study reveals that having diabetes, exposure to traffic-related air pollution (in the form of nitrogen dioxide), and frequent alcohol intake are the most detrimental modifiable risk factors (MRF) for this vulnerable brain network.
It also uncovered significant genetic associations linked to diseases like schizophrenia, Alzheimer’s and Parkinson’s. These findings could inform strategies to mitigate neurodegeneration by targeting the lifestyle factors that put brain health at risk.
Elliott’s international collaboration included researchers from the Pacific Parkinson’s Research Centre at UBC, the University of Oxford, the University of Turin as well as Master’s student Joosung Min from SFU. Their research, The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease, was published in Nature Communications.
We spoke with professor Elliott about his research.
Tell us about the vulnerable brain region you studied. Why it is significant to understanding the development of schizophrenia as well as Alzheimer’s?
Our work examines the “last in first out” (LIFO) network, which was identified by Dr. Gwenaëlle Douaud 10 years ago. This network is a collection of brain areas and primarily includes higher-order areas such as the lateral prefrontal cortex and the medial temporal lobe.
The LIFO network has a unique aging trajectory. It continues to mature relative to other networks until middle adulthood (last in) and then begins to degenerate faster than other networks (first out). Schizophrenia tends to first occur during the period in which LIFO matures, and Alzheimer’s during the period in which LIFO degenerates. Brain areas implicated in both diseases have a large overlap with LIFO. Our understanding of schizophrenia and Alzheimer’s may be improved if we discovered the mechanism behind LIFO’s extended development period and early degeneration.
Can you explain the last in first out hypothesis in relation to this brain network?
There is a theory in gerontology that healthy degeneration mirrors human development. Biological systems supporting this theory unwind later in the lifespan in the opposite way that they first form. The LIFO brain network is a biological system that exemplifies this hypothesis, with the maturity of the network showing remarkable symmetry around an average age of 40.
Based on this research, are there policy recommendations to promote better brain health as people age? What can individuals do to ensure their brains remain as healthy as possible?
To ensure our brains age healthily, our research suggests that we should eat a balanced diet, drink only moderately or not at all, and protect ourselves from traffic-related air pollution. Of these, traffic-related air pollution is a collective responsibility, as well as an individual responsibility. So, policies that strengthen alternatives to gas-powered cars—for example, safer bike lanes—may lead to healthier brain aging.
Tell us more about UK Biobank. Are subjects being added and updated regularly?
UK Biobank is a prospective longitudinal study following the life course of half a million people in the UK. Researchers can gain access to UK Biobank data by proposing a health science experiment within the scope of the consortium. There are regular follow-ups with the participants, and the number of participants who have contributed brain imaging is continually increasing.
Where will you go next with your research using UK Biobank?
I will continue supporting projects at the Wellcome Centre for Integrative Neuroimaging and bringing my network at SFU into the collaboration. My new topics are long COVID, and novel brain imaging modalities. I am also starting a project with Lin Zhang (a professor in statistics and actuarial science at SFU) on making the statistics for genetic studies more inclusive of participants with variation in sex chromosomes, sex and gender.
Is your data analysis open access—and where can we go for more information?
The manuscript is open access, and the code and summary statistics for the data are available here.
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